Biography:

Arije Ghannam, MD PhD is Doctor of Medicine, Immunologist. She obtained her doctorate in immunology at Université Claude Bernard Lyon1, and trained in innate immunity. her scientific career in immunology was developed on complement and kinins, with special emphasis on inflammation associated diseases. She is expert for kinin system, with innovative activity and licensed patents, and was awarded for OSEO innovation prize 2012. She manages the scientific team in KininX, defines and implements R&D programs

Abstract:

The emergence of clinical Angioedema (AE) is subsequent to Bradykinin (BK) production, with AE attacks resulting from a local endothelial permeability in the affected tissue. Kallikrein-Kinin System (KKS) and BK generation mediate this process. AE with normal C1Inhibitor (C1Inh) is difficult to diagnose. It is known to be unresponsive to treatment with antihistamines, corticosteroids, and epinephrine. AE with normal C1Inh is divided between patients with a known F12 mutation and recently with plasminogen or angiopoietin mutations and those with unknown origin. However, when the patient presents with an acute crisis, the biological profile is of great support for the decision of treatment and follow-up. Here we describe four patients admitted at the acute phase of angioedema in emergency department: abdominal cramps, respiratory distress, AE of the eyelids, tongue and lips. The diagnosis was often delayed. Despite the fact that one of the patients needed tracheal intubation in the past, he suffered from recurrent AE, without diagnosis, for the last 25 years. We believe that KKS biological workup is helpful. Three samples were harvested at different times during the attack and investigated. C1 Inhibitor (C1Inh) function, spontaneous amidase activity, kinin measurement and kininogen cleavage were analyzed as described previously. The results demonstrate that KKS activation and subsequently BK production are the key actors of these attacks, without decrease of C1Inh function. They also demonstrated a very important increased kinin forming process with increased spontaneous amidase activity in line with kininogen (HK) cleavage. In addition, the administration C1Inh concentrate results in clinical improvement. The symptomatology of angioedema is subsequent to the enzymatic activity responsible for kinin production. Kinetics of biological events demonstrates KKS activation and BK production. Laboratory confirmation using KKS biological parameters seems to be helpful for diagnosis and patients management

Biography:

Soma Mondal Ghorai has completed her PhD from University of Delhi and currently working as Assistant Professor in the Department of Zoology, Hindu College, University of Delhi, India. She has published more than 10 papers in reputed journals and has been actively involved in research in Comparative Immunology

Abstract:

Toll‐Like Receptors (TLRs) are most studied class of Pattern Recognition Receptors (PRRs) which recognize exogenous Pathogen‐Associated Molecular Patterns (PAMPs) and endogenous Damage-Associated Molecular Patterns (DAMPs) and are prime sentinels of innate immunity. Reptiles being the non-conventional model organisms remain a under deprived class in the study of structure, function and ligand specificity of TLRs except few studies published very recently. Among them, TLR5 is the only protein sensing receptor playing an inevitable role in the signaling cascade involved in innate immunity by recognizing bacterial flagellin. The unavailability of structural and ligand binding information of this receptor till date; directed us to model its ligand binding domain and docking with flagellin. Presence of several homologous proteins having considerable identity and coverage enabled us to construct a reliable 3D model of TLR5 ligand binding domain of Indo-Asian wall lizard Hemidactylus flaviviridis (hfTLR5). Experimentally, solved crystal structure of Zebrafish TLR5-N14VLR in complex with Bacillus subtilis flagellin (bsflagellin) was used as template to carry out template based molecular docking studies. Comparative analysis of docking energies and protein–ligand interactions of all the ligands revealed that bsflagellin residues interact with hfTLR5 ligand binding domain through hydrogen-bonds and hydrophobic interactions positionally segregated at two interfaces which lie in previously reported potential interacting region of TLR5. The described side chain of hot spot residue bsflagellin ‘R89’ was found to make maximum contacts and is shown inserted within the cavity formed by hfTLR5 interacting residues. Out of six, three residues of hfTLR5 (H264, G267 and N274) were found to be conserved in almost all the vertebrate classes and four out of six residues of flagellin were found to be identical in flagellins of TLR5 activating bacteria. The complex thus obtained may help us to better understand the functioning of hfTLR5, thereby bridging the gap in the evolution of species-specific host-microbe interactions